Blood measuring instrument

ABSTRACT

A blood measuring instrument for measuring a specific component of blood. The instrument has a platelike chip ( 2 ) for sucking sampled blood, and a measuring instrument body ( 1 ) including a connector ( 3 ) into which the chip ( 2 ) is plugged. The chip ( 2 ) has an enzyme electrode for delivering a response current when the enzyme reacts with a specific component of the blood. The measuring instrument body ( 1 ) includes two sets of connection terminals ( 21, 22 ) capable of being in contact with lead terminals on the chip ( 2 ), and the connection terminals ( 21, 22 ) of each set are opposed to each other. Therefore, the chip ( 2 ) can be plugged into the connector ( 3 ) and one of the connection terminals of each set can be brought into contact with the lead terminal even if the chip is upside down.

FIELD OF THE INVENTION

The present invention relates to an instrument for measuring theconcentration of a specific component of blood, in particular, to ablood sugar determining instrument for measuring the concentration ofglucose in blood.

BACKGROUND OF THE INVENTION

In recent years, various kinds of biosensors utilizing a specificcatalytic action of enzymes have been developed to be used for clinicalpurposes. Most valuable use of such biosensors may be made in the areaof e.g. diabetes treatment where it is vital for patients to keep theirblood glucose concentration (“blood sugar level” below) within a normalrange. For an inpatient, the blood sugar level can be kept normal underthe supervision of the doctor. For an outpatient, self-control of theblood sugar level is an important factor for treatment in lack ofdoctor's direct supervision.

The self-control of the blood sugar level is achieved through a diet,exerciseand medication. These treatments may often be simultaneouslyemployed under the supervision of the doctor. It has been found that theself-control works more effectively when the patient himself is able tocheck whether or not his blood sugar level is within the normal range.

Recently, blood sugar determining instruments have been used forself-checking of blood sugar level. As shown in FIG. 1, a blood sugardetermining instrument mainly includes a main detecting unit 1 and achip 2 for blood sugar measurement. As shown in FIGS. 2 and 3, the chip2 includes a strip-like substrate 15 provided in its front portion withan electrode section 4. The electrode section 4 is covered by a reactionlayer 5, a spacer 6 and a cover sheet 7. The electrode section 4 isprovided with an operational terminal 11 and a counterpart terminal 12surrounding the operational terminal 11. The operational terminal 11 andthe counterpart terminal 12 are electrically connected to lead terminals13 and 14, respectively, which are formed on a base end portion of thesubstrate 15. The reaction layer 5, which covers the electrode section4, contains potassium ferricyanide and an oxidase such as glucoseoxidase.

The blood measuring instrument may be used in the following manner. Apatient pricks his or her own skin with e.g. a lancet for oozing blood.Then, the oozed-out blood is caused to touch the tip of the chip 2plugged into the detecting unit 1. The blood is partially sucked intothe reaction layer 5 by capillary action. The reaction layer 5, disposedabove the electrode section 4, is dissolved by the blood, which startsan elementary reaction.

The potassium ferricyanide contained in the reaction layer 5 is reduced,whereas potassium ferrocyanide or reduced electron carrier isaccumulated. The amount of the potassium ferrocyanide is proportional tothe concentration of glucose to be measured. When the potassiumferrocyanide accumulated for a specific time is electrochemicallyoxidized by application of a certain voltage, a response current willpass through the operational terminal 11. Thus, the glucoseconcentration (blood sugar level) is determined by measuring theresponse current with the detecting unit 1. As shown in FIG. 6a, thechip 2 is plugged into a connector 3. The connector 3 is internallyprovided with connection terminals 21 to come into contact with the leadterminals 13, 14 for detection of the response current flowing throughthe operational terminal 11. The detected current is converted into aglucose concentration value by a computer incorporated in the detectingunit 1.

The terminals 11, 12, 13, 14 on the chip 2 are formed only on one sideof the chip 2, so that these terminals 11, 12, 13, 14 are readily formedby screen printing. Thus, the manufacturing process is preferablysimplified, which serves to lower the costs of consumable chips.

However, the one-side formation of the terminals 11, 12, 13, 14 can bedisadvantageous in inserting the chip 2 into the connector 3 of thedetecting unit 1 upside down. As shown in FIG. 6b, the lead terminals13, 14 on the chip 2 may fail to be connected to the connectionterminals 21 in the connector 3. In such an instance, proper measurementcannot be performed by the blood sugar determining instrument.

Diabetics may often be elderly people and/or have weak eyes, so thatmany of them may have difficulty in distinguishing one surface of thechip 2 from the other. In light of this, the chip 2 may be provided withside-discerning means. For instance, the chip 2 may be provided with acut out or protrusion formed on one side. Alternatively, the measuringinstrument may be so arranged that the chip 2, when held upside down,cannot be inserted into the detecting unit. In any case, the chip needsto be inserted properly, i.e., without having its obverse and reversesurfaces turned over. Disadvantageously, the formation of a cutout orprotrusion will require additional steps for making the chips, whichresults in a cost increase.

It is an object of the present invention to provide a blood measuringinstrument, wherein a chip can be inserted into a detecting unit withoutundergoing the surface-discerning step.

SUMMARY OF THE INVENTION

A blood measuring instrument according to the present inventioncomprises: a plate-like chip for drawing sampled blood; and a maindetecting unit having a connector into which the chip is inserted. Thechip includes, on a single side, an enzyme electrode section for passinga response current in response to a specific component of the blood, andlead terminals electrically connected to the enzyme electrode section.The main detecting unit includes two sets of connection terminals whichare disposed within the connector and engageable with the lead terminalsof the chip, wherein the two sets of connection terminals are heldinfacing relation to each other.

According to the present invention, the connector of the main detectingunit is internally provided with two sets of connection terminalsengageable with the lead terminals on the chip, and these two sets ofconnection terminals are held in facing relation to each other. When thechip is plugged into the connector, either one of the two sets ofconnection terminals is connected to the lead terminals formed on aselected side of the chip. Thus, proper blood measurement is carried outwhether the chip inserted into the main detecting unit faces upward ordownward.

In a preferred embodiment, the enzyme electrode section includes areaction layer dissolved by the blood and an electrode pattern which hasan operational terminal for passing the response current and acounterpart terminal surrounding the operational terminal. The reactionlayer covers the operational terminal of the electrode pattern.

When the blood is applied onto the chip, the reaction layer is dissolvedby the blood, which starts an enzyme reaction. Thus, electron carriersare generated correspondingly to the concentration of the specificcomponent (e.g. glucose) of the blood. After a certain period of time, avoltage is applied to the chip, whereby a response current is generatedin the operational terminal of the electrode section. For measurement,the response current is supplied to the main detecting unit through thelead terminals and the connection terminals of the connector. Theresponse current is proportional to the concentration of the specificcomponent of the blood. Thus, the concentration of the specificcomponent is calculated on the basis of the response current value byusing a calibration curve prepared beforehand.

In a preferred embodiment, the reaction layer contains glucose oxidaseor lactate oxidase as an oxidase and potassium ferricyanide as anelectron acceptor.

For determining the glucose concentration in blood (blood sugar), theoxidase in the reaction layer is glucose oxidase and the electroncarrier is potassium ferricyanide. In enzyme reaction, the glucose isturned to be gluconic acid, while the potassium ferricyanide is reducedto potassium ferrocyanide. The amount of potassium ferrocyanide isproportional to the concentration of the glucose to be measured. After apredetermined period of time, the potassium ferrocyanide iselectrochemically oxidized by applying a voltage to the chip. Then, theresulting response current is converted to the glucose concentration.

For determining the lactic acid concentration, the oxidase in thereaction layer is lactate oxidase, while the electron carrier ispotassium ferricyanide. In enzyme reaction, the lactic acid is turned tobe pyruvic acid, while the potassium ferricyanide is reduced topotassium ferrocyanide. The amount of the potassium ferrocyanide isproportional to the concentration of the lactic acid to be measured.After a certain time, the potassium ferrocyanide is electrochemicallyoxidized by applying a voltage to the chip. Then, the amount of theresulting response current is converted to the lactic acidconcentration.

As described above, according to the blood measuring instrument of thepresent invention, it is unnecessary to worry about whether or not thechip is held upside down in inserting the chip into the connector of themain detecting unit. It is much easier for weak-sighted or elderlypatients to use the blood measuring instrument of the present inventionthan the conventional instrument, since there is no need to check theorientation of the obverse or reverse surface of the chip.

Other features and advantages of the present invention will becomeapparent from the detailed description given below with reference to theaccompanying drawings.

BRIEF DESCRIPTION OF THE DRAWINGS

FIG. 1 is a perspective view showing the external appearance of a bloodmeasuring instrument according to an embodiment of the presentinvention.

FIG. 2 is a perspective view showing the entirety of a chip used for theblood measuring instrument.

FIG. 3 is an exploded, perspective view showing the chip used for theblood measuring instrument.

FIGS. 4a and 4 b are enlarged, partial sectional views showing how thechip engages with a main detecting unit of the blood measuringinstrument of the present invention.

FIG. 5 is a block diagram showing an example of control circuit for theblood measuring instrument of the present invention.

FIGS. 6a and 6 b are enlarged, partial sectional views illustrating howthe chip and the main detecting unit of a conventional blood measuringinstrument.

BEST MODE FOR CARRYING OUT THE INVENTION

An embodiment of the present invention will be described with referenceto the accompanying drawings. As shown in FIG. 1, a blood measuringinstrument includes a main detecting unit 1 and a disposable plate-likechip 2 to be plugged into the main detecting unit 1 in use.

In carrying out the present invention, the conventional basicarrangements may be applicable to the chip 2 without any changes. Asshown in FIGS. 2 and 3, the chip 2 has a strip-like shape as a whole,while also including a surface whose front end portion is provided withan enzyme electrode section 10 and whose base end portion is providedwith two lead terminals 13, 14. Preferably, the lead terminals 13, 14may be made of silver. The enzyme electrode section 10 includes anelectrode pattern 4 and a reaction layer 5 arranged thereon. Theelectrode pattern has a carbon operational terminal 11 and a carboncounterpart terminal 12 surrounding the operational terminal. Theoperational terminal 11 is electrically connected to one lead terminal13, while the counterpart terminal 12 is electrically connected to theother lead terminal 14. The terminals 11, 12, 13, 14 may be formed byscreen printing on a substrate made of poly(ethylene terephthalate). Aspacer 6 and a cover sheet 7 are attached to cover the reaction layer 5.The spacer is formed with a slit 16 open at the front end portion, whilethe cover sheet 7 is formed with an air hole 17. Thus, after beingapplied onto the tip of the chip 2, sample liquid such as blood issucked into the passage of the slit 16 by capillary action and led tothe reaction layer 5.

The reaction layer 5 is a plate-like element made of dried aqueoussolution containing oxidase (glucose oxidase), potassium ferricyanideand carboxymethyl cellulose.

The main detecting unit 1 is provided with a connector 3 into which thebase end portion of the chip 2 is inserted. According to the presentinvention, the connector 3 is internally provided with two sets ofconnection terminals 21, 22 arranged in facing relation. In theillustrated embodiment, each set of the connection terminals 21, 22includes two terminals. Thus, the lead terminals 13, 14 formed on thebase end portion of the chip 2 are brought into proper contact withthese terminals whether the obverse surface of the chip 2 faces upwardor downward in insertion.

In use, the chip 2 is plugged into the connector 3 of the main detectingunit 1. According to the present invention, as described above, it doesnot matter whether the chip 2 faces upward or downward in insertion.Then, a cut is made in the skin with e.g. a lancet to ooze out a smallamount of blood therefrom. Then, the blood is touched by the tip of thechip 2. The blood is then led to the enzyme electrode section 10 of thechip 2 by capillary action, as described above.

The reaction layer 5 of the enzyme electrode section 10 is dissolved bythe supplied blood. Then, according to the enzyme reaction representedby the following formula, potassium ferrocyanide is produced in anamount corresponding to the glucose concentration. After a certainperiod of time, a predetermined voltage is applied on the chip 2. Inresponse, a current is generated, which is proportional to theconcentration of the potassium ferrocyanide produced by the enzymereaction or to the concentration of the glucose. Therefore, the bloodsugar level can be known by measuring the response current.

FIG. 5 shows an example of control circuit of the blood sugardetermining instrument. When the chip 2 is plugged into the connector 3,a plugged-electrode sensing switch 50 detects the insertion of the chip,whereby a switch 51 is turned on automatically. Thus, a predeterminedvoltage is applied to the operational terminal 11 of the chip 2, whichis electrically connected to the connection terminal 21 or connectionterminal 22. The voltage to be applied is provided by a battery 55. Theresponse current generated in the chip 2 set into the connector 3 isconverted to voltage by a current/voltage converter 56 and then suppliedto an A/D converter 57. A microcomputer 58 reads out an output signalfrom the A/D converter 57.

The enzyme electrode section of the chip 2 can be regarded as aresistor. When the resistance of the chip 2 is R_(s), the amplificationresistance of the current/voltage converter 56 is R_(f), and the appliedvoltage is E, then the output voltage E₀ of the current/voltageconverter 56 is given by the following equation:

E ₀ =E+i×R _(f) =E+(E/R _(s))×R _(f)

When no blood is supplied, the resistance R_(s) of the chip 2 isextremely large or substantially infinite, while the current i is verysmall. Accordingly, the output voltage E₀ of the current/voltageconverter 56 is nearly equal to E.

When blood is supplied to the chip 2, on the other hand, the resistanceR_(s) of the chip 2 decreases sharply, which causes a sharp increase inE₀. The absorption of the blood is detected by continuously monitoringthe output voltage E₀ of the current/voltage converter 56.

Variations of the output voltage E₀ of the current/voltage converter 56are analyzed by the microcomputer 58 via the A/D converter 57. Thus,upon sharp increase of E₀ (or sharp decrease of R_(s)), the timer of themeasuring instrument is automatically started. At the same time, theswitch 51 is turned off. The once-opened switch 51 is closed againlater, namely, after the above-mentioned enzyme reaction has occurred.Thus, required voltage is applied to the operational terminal 11. Then,the response current generated at this stage is measured to be used forcalculation of glucose concentration based on a prescribed calibrationcurve. The result is displayed on a display 59.

In the above embodiment, the blood measuring instrument of the presentinvention determines the concentration of glucose in blood (bloodsugar). However, the same blood measuring instrument may be applicableto determinations of other components. When the oxidase contained in thereaction layer 5 is lactate oxidase, the blood measuring instrument canbe utilized for determination of the lactic acid concentration. In thiscase, the chip may be supplied with saliva since an appropriate amountof lactic acid is secreted in saliva. Though saliva has a weaker bufferaction than blood, it is possible to determine the lactic acidconcentration of saliva when buffer agent is added to the reaction layer5 of the chip 2.

As shown in FIGS. 2 and 3, the electrode pattern 4 of the chip 2 isformed on the front end portion of the strip-like substrate 15, and theelectrode pattern 4 is covered by the reaction layer 5, spacer 6, andcover sheet 7. The electrode pattern 4 includes the operational terminal11 and the counterpart terminal 12 surrounding the operational terminal11. The operational terminal 11 and the counterpart terminal 12 areelectrically connected to the lead terminal 13 and the lead terminal 14,respectively, which are formed on the base end portion of the substrate15. The reaction layer 5 covering the electrode pattern 4 containspotassium ferricyanide and an oxidase or glucose oxidase.

Without being limited to the above, the present invention may be variedin many ways within the scope of the appended claims, and the variationmay include equivalent replacement each element.

What is claimed is:
 1. A blood measuring instrument comprising: aplate-like chip for drawing sampled blood; and a main detecting unithaving a connector into which the chip is inserted; wherein the chipincludes, on a single side, an enzyme electrode section for passing aresponse current in response to a specific component of the blood, andlead terminals electrically connected to the enzyme electrode section;and wherein the main detecting unit includes two sets of connectionterminals which are disposed within the connector and engageable withthe lead terminals of the chip, the two sets of connection terminalsbeing spaced from each other in a thickness direction of the chip andheld in facing relation to each other.
 2. The blood measuring instrumentaccording to claim 1, wherein the enzyme electrode section comprises areaction layer dissolved by the blood and an electrode pattern whichincludes an operational terminal for passing the response current and acounterpart terminal surrounding the operational terminal, the reactionlayer covering the operational terminal of the electrode pattern.
 3. Theblood measuring instrument according to claim 1, wherein the reactionlayer contains glucose oxidase as an oxidase and potassium ferricyanideas an electron acceptor.
 4. The blood measuring instrument according toclaim 1, wherein the reaction layer contains lactate oxidase as anoxidase and potassium ferricyanide as an electron acceptors.